Graphical Abstract:

Abstract:

Background: The voltage-dependent anion channels (VDAC) play an essential role in
the cross talk between mitochondria and the rest of the cell. Their implication in cell life and cell
death has been studied extensively in recent years. In this work we studied the impact of mitochondrial
membrane (VDACs) on cell survival and response to X-ionizing radiation (IR) of human
lymphoblastoid K562 cells.

Methods: The inhibition of VDACs was achieved by 4,4`-diisothiocyanostilbene-2,2`-disulfonic
acid (DIDS) inhibitor and in vitro experiments including clonogenity assay, UV-visible spectrophotometry,
comet assay and FACS analysis were implemented.

Results: Inhibition of VDAC led to augmentation of IR-induced apoptosis and ROS production.
Additionally, DIDS affected repair of IR-induced DNA strand breaks and was in line with both induction
of apoptosis and caspase activity. The IR-induced NO production was potently reduced by
inhibition of VDAC.

Conclusion: Our results suggest that VDAC control cellular response to ionizing radiation through
modulation of the ROS- and NO-dependent signaling pathways. Inhibition of VDAC with DIDS
induced apoptosis in irradiated K562 lymphoblastoid cells points at DIDS, as a promising agent to
enhance the effectiveness of radiotherapy.

Abstract:Background: The voltage-dependent anion channels (VDAC) play an essential role in
the cross talk between mitochondria and the rest of the cell. Their implication in cell life and cell
death has been studied extensively in recent years. In this work we studied the impact of mitochondrial
membrane (VDACs) on cell survival and response to X-ionizing radiation (IR) of human
lymphoblastoid K562 cells.

Methods: The inhibition of VDACs was achieved by 4,4`-diisothiocyanostilbene-2,2`-disulfonic
acid (DIDS) inhibitor and in vitro experiments including clonogenity assay, UV-visible spectrophotometry,
comet assay and FACS analysis were implemented.

Results: Inhibition of VDAC led to augmentation of IR-induced apoptosis and ROS production.
Additionally, DIDS affected repair of IR-induced DNA strand breaks and was in line with both induction
of apoptosis and caspase activity. The IR-induced NO production was potently reduced by
inhibition of VDAC.

Conclusion: Our results suggest that VDAC control cellular response to ionizing radiation through
modulation of the ROS- and NO-dependent signaling pathways. Inhibition of VDAC with DIDS
induced apoptosis in irradiated K562 lymphoblastoid cells points at DIDS, as a promising agent to
enhance the effectiveness of radiotherapy.